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Evaluating Evidence of Low-Dose Toxicity

Katrina Waters, PNNL

On July 18, the National Academies of Science, Engineering, and Medicine released a study report on a strategy to improve the ability of regulators to evaluate concerns that certain chemicals might cause hormone-related health effects at low doses.

Among the 11 co-authors - from industry, academe, and research centers - was biochemist Katrina Waters, division director for Biological Sciences. Her many research interests include integrating diverse biological data for predictive modeling of disease pathways and host-pathogen interactions.

Federal agencies commission and fund such reports, using the National Academies as a kind of independent consulting firm capable of addressing important issues in science, engineering, and medicine. The last such report Waters co-authored was commissioned by the Department of Defense.

Endocrine active chemicals (EACs) are a class of chemicals capable of interfering with endocrine (hormone) systems. Even small changes in hormone concentrations, particularly during sensitive life changes, can have lasting effects. The EPA regulates EACs and other toxic chemicals as part of its mission.

The report's authors developed a strategy for evaluating evidence of low-dose effects of EACs, also known as hormone disruptors. They recommended three successive steps: surveillance, investigation and analysis, and actions.

They chose two EACs as case studies, or "example systematic reviews." The first focused on phthalates, a class of ubiquitous contaminants known to affect the androgen hormone system, which plays a critical role in the development of the male reproductive tract.

The second focused on polybrominated diphenylethers (PBDEs), another class of similarly ubiquitous environmental contaminants that are linked to deficits in learning, memory, intelligence, and to attention-related behavioral conditions.

The committee demonstrated that meta-analyses of animal data were useful for assessing confidence in the evidence and that such data helped characterize dose-response relationships. They also found that systematic reviews underscored the importance of taking a multidisciplinary approach to data analysis, and pointed to the challenges of integrating data from human and animal studies.